Gamma Wave Stimulation Affects BACE1 Levels and Promotes the Transition of Microglia from M1 State to M2 State
DOI:
https://doi.org/10.61173/sv9bta14Keywords:
Alzheimer’s disease, BACE1, amyloid-beta, microglia, gamma wave stimulation, neuroinflammation, M1, M2 polarization, cognitive function, Aβ plaquesAbstract
Alzheimer’s disease (AD) is a devastating neurodegenerative disorder and it presents with the hallmark neuropathological features of amyloid-beta (Aβ) plaques, tau tangles and active neuroinflammation. Beta-site amyloid precursor protein cleaving enzyme 1 (BACE-1), a key mediator of increased Aβ, has been identified as the primary enzymatic source for production of this pathologic peptide while reactive microglial cells contribute to ongoing neurodegeneration perhaps through activation into their aggressive M1 state. The present study endeavors for the first time to address how gamma wave stimulation modulates BACE1 and microglial polarization (from M1 to beneficial M2) in different AD models. We hypothesize that gamma wave stimulation will reduce BACE1, decrease Aβ plaque burden and shift microglials towards M2 phenotype leading to reduced neuroinflammation and maintain cognitive function. This study will target mouse models of AD which have undergone gamma wave stimulation and its effects on BACE1 expression, microglial polarisation markers, Aβ plaque load and cognitive performance. Hypotheses the treatment will reduce BACE1 activity, decrease M1/M2 microglial ratio, improve cognitive performance and delay Aβ plaque accumulation These data suggest promising therapeutic strategies for neuroinflammation and amyloidogenesis in AD.
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